Efficacy of tricaine methanesulfonate (MS-222) as an anesthetic agent for blocking sensory-motor responses in Xenopus laevis tadpoles

PLoS One. 2014 Jul 1;9(7):e101606. doi: 10.1371/journal.pone.0101606. eCollection 2014.


Anesthetics are drugs that reversibly relieve pain, decrease body movements and suppress neuronal activity. Most drugs only cover one of these effects; for instance, analgesics relieve pain but fail to block primary fiber responses to noxious stimuli. Alternately, paralytic drugs block synaptic transmission at neuromuscular junctions, thereby effectively paralyzing skeletal muscles. Thus, both analgesics and paralytics each accomplish one effect, but fail to singularly account for all three. Tricaine methanesulfonate (MS-222) is structurally similar to benzocaine, a typical anesthetic for anamniote vertebrates, but contains a sulfate moiety rendering this drug more hydrophilic. MS-222 is used as anesthetic in poikilothermic animals such as fish and amphibians. However, it is often argued that MS-222 is only a hypnotic drug and its ability to block neural activity has been questioned. This prompted us to evaluate the potency and dynamics of MS-222-induced effects on neuronal firing of sensory and motor nerves alongside a defined motor behavior in semi-intact in vitro preparations of Xenopus laevis tadpoles. Electrophysiological recordings of extraocular motor discharge and both spontaneous and evoked mechanosensory nerve activity were measured before, during and after administration of MS-222, then compared to benzocaine and a known paralytic, pancuronium. Both MS-222 and benzocaine, but not pancuronium caused a dose-dependent, reversible blockade of extraocular motor and sensory nerve activity. These results indicate that MS-222 as benzocaine blocks the activity of both sensory and motor nerves compatible with the mechanistic action of effective anesthetics, indicating that both caine-derivates are effective as single-drug anesthetics for surgical interventions in anamniotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminobenzoates / pharmacology*
  • Anesthetics / pharmacology*
  • Animals
  • Benzocaine / pharmacology
  • Evoked Potentials / drug effects*
  • Larva
  • Motor Neurons / physiology*
  • Sensory Receptor Cells / physiology*
  • Xenopus laevis


  • Aminobenzoates
  • Anesthetics
  • tricaine
  • Benzocaine

Grant support

The authors CR FB BPC and HS acknowledge financial support from the German Science Foundation (CRC 870, TP B12), the German Federal Ministry of Education and Research under the Grant code 01 EO 0901, the Munich Center for Neurosciences - Brain and Mind (MCN) and the Graduate School for Systemic Neurosciences (GSN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.